1. HANDBOOK OF DYSLIPIDEMIA AND ATHEROSCLEROSIS Part One Professor Jean-Charles Fruchart Department of Atherosclerosis (Inserm UR545) Pasteur Institute of Lille University of Lille II France

2.  The global epidemic of modern living ATHEROSCLEROSIS

3. Cardiovascular disease is the leading cause of death among adults worldwide (1996) Coronary disease7.2 million Cancer6.3 Cerebrovascular disease4.6 Acute lower respiratory tract infections3.9 Tuberculosis3.0 COPD (chronic obstructive pulmonary disease)2.9 Diarrhea (including dysentery)2.5 Malaria2.1 AIDS1.5 Hepatitis B1.2

4. Coronary mortality: alarming worldwide forecasts

5. Atherosclerosis: a multifactorial disease

6. Main risk factors for coronary heart disease

7. Global projections for the diabetes epidemic: 1995-2010

8. Atherosclerosis

9.  The stages of development of atherosclerosis PATHOPHYSIOLOGY

10. Arterial wall: structure and function

11. Different stages of atherosclerotic plaque development

12. Vascular endothelium modification in atherosclerosis

13. Plaque formation 1 — Fatty streak

14. Plaque formation 2 — Fibrous cap

15. Plaque formation 3 — Lipid core

16. From plaque to thrombosis, key event: plaque rupture

17.  The role of the macrophage PATHOPHYSIOLOGY

18. Plaque vulnerability Key role of macrophages

19. Vulnerable plaque Key role of the macrophage in vascular wall inflammation

20. Fibrinogen is an independent risk factor for atherosclerosis

21. Vulnerable plaque Key role of the macrophage in the degradation of the fibrous cap

22. Thrombus formation The macrophages release coagulation factors

23. Tissue factor: the initiator of coagulation and thrombogenesis in vivo

24. Oxidized LDL and thrombogenesis

25. Plaque disruption (plaque cracking, fissuring, rupture – thrombosis start point)

26.  The role of atherogenic lipoproteins PATHOPHYSIOLOGY

27. Lipid core constitution Activated macrophages accumulate lipids

28. Lipid core constitution LDL oxidation

29. Parietal vascular inflammation The activated macrophage produces inflammatory cytokines

30. Parietal vascular inflammation NF  B action in the inflammation process

31.  The influence of risk factors PATHOPHYSIOLOGY

32. Diabetes and atherosclerosis

33. Tobacco and atherosclerosis

34. Dyslipidemia and atherosclerosis

35. HTN, hemodynamic factor and atheroclerosis

36. How to reduce plaque formation Intervention on risk factors

37.  The goals of treatment PATHOPHYSIOLOGY

38. How to reduce the risk of plaque rupture

39. How to reduce the risk of thrombosis

40. ~10% Weight loss = ~30% Visceral adipose tissue loss

41. Characteristics of an unstable plaque

42. Plaque vulnerability factors Intrinsic factors

43. Modification of extrinsic vulnerability factors

44. Plaque rupture The main releasing factors

45.  Synthesis and transport PHYSIOLOGY OF LIPIDS AND LIPOPROTEINS

46. Classification of lipids and lipoproteins

47. Characteristics of lipoproteins

48. Triglyceride-rich lipoproteins: size, structure and composition

49. Digestion and metabolism of dietary fat

50. HDL metabolism and reverse cholesterol transport

51. Cholesterol efflux and reverse cholesterol transport is modulated by two receptors

52. Atherogenicity of small dense LDL

53.  Atherogenicity PHYSIOLOGY OF LIPIDS AND LIPOPROTEINS

54. Size and apolipoprotein composition are the main factors determining atherogenicity of triglyceride-rich particles

56. Apo C-III modulates VLDL

57. Apo C-III in apo B particles is atherogenic

58. Relationship between apo C-III in apo B containing lipoproteins and atherogenicity

59. PROCAM Study MI-Incidence according to LDL-cholesterol and triglycerides

60. PROCAM Study CHD risk according to LDL-C and TG increased TG confers raised CHD risk at all levels of LDL-C

61. HDL: an anti-atherogenic lipoprotein

62. HDL metabolism: 5 key genes

63. HDL: apo AI-rich particles

64. Apo A-I protects against atherosclerosis

65. Apo A-II protects against atherosclerosis The human apo A-II transgenic mouse model